This invention relates to novel benzimidazole derivatives, pharmaceutical compositions containing them, and methods of using them to treat certain central nervous system (CNS) and other disorders. The compounds of this invention are corticotropin releasing factor (CRF) receptor antagonists.
CRF antagonists are referred to in U.S. Pat. Nos. 4,605,642 and 5,063,245, which relate, respectively, to peptides and pyrazolinones, and were issued, respectively, on Aug. 12, 1986 and Nov. 5, 1991. They are also referred to in the following: PCT patent application No. PCT/IB95/00439, which designates the United States and was filed on Jun. 6, 1995; PCT patent application No. PCT/IB95/00373, which designates the United States and was filed on May 18, 1995; U.S. patent application No. 08/448,539, which was filed in the PCT on Nov. 12, 1993 and entered the U.S. national phase on Jun. 14, 1995; U.S. patent application No. 08/481,413, which was filed in the PCT on Nov. 26, 1993 and entered the U.S. national phase on Jul. 24, 1995; and U.S. patent application No. 08/254,820, which was filed on Apr. 19, 1995. All the foregoing patents and patent applications are incorporated herein by reference in their entireties.
The importance of CRF antagonists Is discussed in the literature, e.q., as discussed in U.S. Pat. No. 5,063,245, which is incorporated herein by reference in its entirety. A recent outline of the different activities possessed by CRF antagonists is found in M. J. Owens et al., Pharm. Rev., Vol. 43, pages 425 to 473 (1991), also incorporated herein by reference. Based on the research described in these two and other references, CRF antagonists are effective in the treatment of a wide range of stress-related illnesses, such as depression, anxiety, headache, irritable bowel syndrome, inflammatory diseases, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, hemorrhagic stress, drug and alcohol withdrawal symptoms, drug addiction, infertility, head trauma, stroke, and stress-induced infections in humans and animals.